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Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis.
World J Gastroenterol 2012; 18(22):2813-20WJ

Abstract

AIM

To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH).

METHODS

We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy, for whom the presence of cirrhosis could be determined based on histological or clinical criteria, without excessive alcohol intake (< 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis. Steatosis was evaluated in 123 patients by histology (n = 100) or ultrasound (n = 23). The PNPLA3 rs738409 single nucleotide polymorphism, encoding for the p.148M protein variant, was genotyped by a Taqman assay (assay on demand, Applied Biosystems). The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis.

RESULTS

PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI), the presence of diabetes, and lipid levels, but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele, 95% confidence interval (CI): 1.05-3.31; P = 0.037], independently of BMI and alanine aminotransaminase (ALT) levels. The p.148M variant was also associated with higher aspartate aminotransferase (P = 0.0014) and ALT levels (P = 0.017) at diagnosis, independently of BMI and the severity of iron overload. In patients with liver biopsy, the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27, P = 0.041). In the overall series of patients, the p.148M variant was associated with cirrhosis in lean (P = 0.049), but not in overweight patients (P = not significant). At logistic regression analysis, cirrhosis was associated with BMI ≥ 25 (OR 1.82, 95% CI: 1.02-3.55), ferritin > 1000 ng/mL at diagnosis (OR 19.3, 95% CI: 5.3-125), and with the G allele in patients with BMI < 25 (OR 3.26, 95% CI: 1.3-10.3).

CONCLUSION

The PNPLA3 I148M polymorphism may represent a permissive factor for fibrosis progression in patients with C282Y+/+ HH.

Authors+Show Affiliations

Università degli Studi di Milano, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, 20122 Milano, Italy. luca.valenti@unimi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22719190

Citation

Valenti, Luca, et al. "Patatin-like Phospholipase Domain Containing-3 Gene I148M Polymorphism, Steatosis, and Liver Damage in Hereditary Hemochromatosis." World Journal of Gastroenterology, vol. 18, no. 22, 2012, pp. 2813-20.
Valenti L, Maggioni P, Piperno A, et al. Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis. World J Gastroenterol. 2012;18(22):2813-20.
Valenti, L., Maggioni, P., Piperno, A., Rametta, R., Pelucchi, S., Mariani, R., ... Fargion, S. (2012). Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis. World Journal of Gastroenterology, 18(22), pp. 2813-20. doi:10.3748/wjg.v18.i22.2813.
Valenti L, et al. Patatin-like Phospholipase Domain Containing-3 Gene I148M Polymorphism, Steatosis, and Liver Damage in Hereditary Hemochromatosis. World J Gastroenterol. 2012 Jun 14;18(22):2813-20. PubMed PMID: 22719190.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis. AU - Valenti,Luca, AU - Maggioni,Paolo, AU - Piperno,Alberto, AU - Rametta,Raffaela, AU - Pelucchi,Sara, AU - Mariani,Raffaella, AU - Dongiovanni,Paola, AU - Fracanzani,Anna Ludovica, AU - Fargion,Silvia, PY - 2011/06/27/received PY - 2012/02/22/revised PY - 2012/02/26/accepted PY - 2012/6/22/entrez PY - 2012/6/22/pubmed PY - 2012/10/24/medline KW - Fatty liver KW - Fibrosis KW - HFE protein KW - Hemochromatosis KW - Iron overload KW - Patatin-like phospholipase domain containing-3 gene KW - Steatosis SP - 2813 EP - 20 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 18 IS - 22 N2 - AIM: To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH). METHODS: We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy, for whom the presence of cirrhosis could be determined based on histological or clinical criteria, without excessive alcohol intake (< 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis. Steatosis was evaluated in 123 patients by histology (n = 100) or ultrasound (n = 23). The PNPLA3 rs738409 single nucleotide polymorphism, encoding for the p.148M protein variant, was genotyped by a Taqman assay (assay on demand, Applied Biosystems). The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis. RESULTS: PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI), the presence of diabetes, and lipid levels, but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele, 95% confidence interval (CI): 1.05-3.31; P = 0.037], independently of BMI and alanine aminotransaminase (ALT) levels. The p.148M variant was also associated with higher aspartate aminotransferase (P = 0.0014) and ALT levels (P = 0.017) at diagnosis, independently of BMI and the severity of iron overload. In patients with liver biopsy, the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27, P = 0.041). In the overall series of patients, the p.148M variant was associated with cirrhosis in lean (P = 0.049), but not in overweight patients (P = not significant). At logistic regression analysis, cirrhosis was associated with BMI ≥ 25 (OR 1.82, 95% CI: 1.02-3.55), ferritin > 1000 ng/mL at diagnosis (OR 19.3, 95% CI: 5.3-125), and with the G allele in patients with BMI < 25 (OR 3.26, 95% CI: 1.3-10.3). CONCLUSION: The PNPLA3 I148M polymorphism may represent a permissive factor for fibrosis progression in patients with C282Y+/+ HH. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/22719190/Patatin_like_phospholipase_domain_containing_3_gene_I148M_polymorphism_steatosis_and_liver_damage_in_hereditary_hemochromatosis_ L2 - http://www.wjgnet.com/1007-9327/full/v18/i22/2813.htm DB - PRIME DP - Unbound Medicine ER -